Over the course of the human life, humans are faced with accumulated oxidative damage. This oxidative damage may cause age-related diseases to manifest, such as Parkinson's, Alzheimer's, and certain types of cancer. Prevention of these diseases may be possible by lowering the amount of reactive oxygen species (ROS) in the body. This can partially be achieved by introducing antioxidants. Fullerenes such as buckminsterfullerene (C60) possess remarkable antioxidant properties. Moussa et al. (Biomaterials 2012, 33, 4936; Biomaterials 2012, 33, 6292) have demonstrated that the lifespan of rats could be doubled by regular administration of C60. Recent studies suggest that C60 administration may prevent the radical cascade in cells, which could lead to an increased lifespan, and to the possible prevention and treatment of cancers and neurodegenerative disorders.
Fullerenes are also promising photosensitizer candidates for use in photodynamic therapy. In photodynamic therapy, a photosensitizer is used which creates singlet oxygen upon local irradiation with light. These singlet oxygen species have toxic effects towards cells and can be used to kill cancer cells. Photodynamic therapy allows for selectively targeting tumor tissue, thereby providing an enhanced selectivity towards cancer cells and fewer side effects compared to radiotherapy and chemotherapy. The current generation of photosensitizers approved by the food and drugs administration (FDA) (Photofrin®, Metvix® and Levulan®) allow only for treatment of the skin or require the patient to stay inside to avoid sun-induced photosensitivity. As C60 requires irradiation with UVA-light, early stage cancers could be eliminated using C60 and endoscopic irradiation, while collateral damage is minimized by the low penetration depth of the UVA-light and the antioxidant activity of C60. Moreover, the low penetration depth of UVA-light and the melanin present in human skin strongly suppress sun-induced photosensitivity. Accordingly, C60 may allow for more selective photodynamic therapy compared to the currently used infrared based photodynamic therapy.
Although fullerenes have promising biomedical applications as antioxidant and as photosensitizer, the extremely low water solubility of these compounds results in a low bioavailability. For example, C60 has a water solubility of only 10−8 ng/L.
In general, three approaches are used to increase the water solubility of fullerenes.
A first methodology is the chemical modification of fullerenes to improve their hydrophilicity. However, this is difficult due to poor control of the regioselectivity and causes disruption of the aromaticity, thereby inducing a reduction of the intrinsic beneficial properties of these compounds.
A second methodology is based on the production of meta-stable dispersions of fullerenes, by co-suspension of fullerenes in an organic solvent and water, whereby after slow removal of the organic solvent meta-stable fullerene clusters are obtained. However, this methodology is time-consuming and residual organic solvents can be toxic. Moreover, the biological activity of the clusters decreases with increasing size of the clusters and their meta-stable state only provides stability for a relatively short time.
A third methodology employs water soluble carriers to dissolve or disperse fullerenes in aqueous environment. This approach avoids toxicity issues caused by residual solvent and does not require chemical modification of the fullerenes, while additional functionalities can be incorporated through the carrier. Nevertheless, this approach is typically plagued by instability of the final product or by long purification procedures to remove organic solvents which are used in the preparation of the product. Moreover, the final product typically has a low fullerene content.
Accordingly, there is a need for improved methods for preparing aqueous fullerene compositions, which mitigate at least one of the problems stated above.